tbuckley/cabot-search huggingface dataset:
No safe harbors for recurrent posterior fossa group A ependymoma: A time for change in risk assignment?
Authors: Jordan R Hansford, David D Eisenstat
Journal: Neuro-Oncology (2023)

Journal Article No safe harbors for recurrent posterior fossa group A ependymoma: A time for change in risk assignment? Get access Jordan R Hansford, Jordan R Hansford Michael Rice Cancer Centre, Women’s and Children’s Hospital, North Adelaide, South Australia, AustraliaPrecision Cancer Medicine, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaSouth Australia Immunogenomics Cancer Institute, University of Adelaide, Adelaide, South Australia, Australia Corresponding Author: Jordan R. Hansford, BScH, MSc, MBBS, FRACP, Michael Rice Cancer Centre, Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia (jordan.hansford@sa.gov.au); Search for other works by this author on: Oxford Academic PubMed Google Scholar David D Eisenstat David D Eisenstat Children’s Cancer Centre, Royal Children’s Hospital, Parkville, Victoria, AustraliaStem Cell Biology, Murdoch Children’s Research Institute, Parkville, Victoria, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, Victoria, Australia David D. Eisenstat, MD, MA, FRCPC, FRACP, Children’s Cancer Centre, The Royal Children’s Hospital Melbourne, 50 Flemington Road, Parkville VIC 3052 Australia (david.eisenstat@rch.org.au). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 10, October 2023, Pages 1868–1870, https://doi.org/10.1093/neuonc/noad129 Published: 24 July 2023 Article history Published: 24 July 2023 Corrected and typeset: 16 August 2023
Abstract ND04: BAY 2965501: A highly selective DGK- ζ inhibitor for cancer immuno-therapy with first-in-class potential
Authors: Rienk Offringa, Catherine Olesch, Frederik Cichon, Mareike Grees, Norbert Schmees, Ulrike Roehn, Florian Prinz, Judith Guenther, Detlef Stoeckigt, Michael Erkelenz, Thi Thanh Uyen Nguyen, Ulf Boemer, Nicolas Werbeck, Marc Kunze, Kirstin Petersen, Dennis Kirchhoff
Journal: Cancer Research (2023)

Abstract The second messenger diacyl glycerol (DAG) plays a key role in T cell receptor downstream signaling and thereby in T-cell activation. Diacylglycerol kinase zeta (DGK-ζ) is a lipid kinase that can down-modulate T-cell activation by catalyzing the conversion of DAG to phosphatidic acid, thereby acting as a ligand independent, intracellular immune checkpoint. Inhibition of DGK- ζ offers the potential to enhance T cell priming against suboptimal tumor antigens and to overcome multiple immune-suppressive mechanisms in the tumor microenvironment. Bayer AG in collaboration with the German Cancer Research Center (DKFZ) have developed BAY 2965501, a highly selective, orally available DGK-ζ inhibitor which shows a unique binding mode and good DMPK profile. The compound enhances the reactivity of human and mouse T-cells, both in the priming and the effector phase, and overcomes the inhibitory impact of suppressive factors, such as adenosine and prostaglandin E2. Oral dosing of BAY 2965501 shows T cell dependent efficacy in syngeneic, murine tumor models. Furthermore, this results in reactivation of exhausted T cells in vivo. Preclinical safety studies showed only mild findings, so that good clinical tolerability is expected. Collectively, the preclinical data support first in human (FiH) phase I testing of therapeutic potential. A FiH trial with BAY 2965501 in patients with advanced solid tumors including NSCLC, gastric/GEJ AdCa, ccRCC, and melanoma patients, is currently enrolling patients (NCT05614102). This study will evaluate the safety, tolerability, maximum tolerated or administered dose, pharmacokinetics, pharmacodynamics, and tumor response profile of BAY 2965501. Citation Format: Rienk Offringa, Catherine Olesch, Frederik Cichon, Mareike Grees, Norbert Schmees, Ulrike Roehn, Florian Prinz, Judith Guenther, Detlef Stoeckigt, Michael Erkelenz, Thi Thanh Uyen Nguyen, Ulf Boemer, Nicolas Werbeck, Marc Kunze, Kirstin Petersen, Dennis Kirchhoff. BAY 2965501: A highly selective DGK- ζ inhibitor for cancer immuno-therapy with first-in-class potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr ND04.
Abstract ND07: Discovery of RMC-6291, a tri-complex KRASG12C(ON) inhibitor
Authors: Jim Cregg, R J. Nichols, Y C. Yang, C J. Schulze, Z Wang, R Dua, J Jiang, N Nasholm, J E. Knox, K Seamon, M Longhi, A Tomlinson, K Chou, S Li, D P. Wildes, M Singh, E S. Koltun, A L. Gill, J A. Smith
Journal: Cancer Research (2023)

Abstract The KRASG12C mutation occurs in 11 - 14% of non-small cell lung cancers, ~4% of colorectal cancers, and ~2% of pancreatic cancers in the U.S., and drives these cancers by shifting the cellular equilibrium of KRAS towards the GTP-bound, active state, KRASG12C(ON). The resulting increased levels of KRASG12C(ON) in turn increase signaling output to initiate and support the oncogenic state. RMC-6291 is a potent, orally bioavailable inhibitor of KRASG12C(ON) that forms a tri-complex within tumor cells along with KRASG12C(ON) and cyclophilin A (CypA), driving a near-immediate disruption of RAS effector binding and extinction of KRASG12C(ON) signaling. RMC-6291 treatment produces deep and durable suppression of RAS pathway activity in KRASG12C tumor models and drives profound tumor regressions in vivo. In a mouse clinical trial with a representative panel of xenograft models of KRASG12C NSCLC, RMC-6291 outperformed adagrasib, displaying a potential ‘best-in-class’ profile with an increased number of responses, greater depth of tumor regressions and improved durability of responses. Thus, RMC-6291 is a clinical stage inhibitor of KRASG12C(ON) that potentially overcomes limitations of first-generation KRASG12C(OFF) inhibitors. Citation Format: Jim Cregg, R J. Nichols, Y C. Yang, C J. Schulze, Z Wang, R Dua, J Jiang, N Nasholm, J E. Knox, K Seamon, M Longhi, A Tomlinson, K Chou, S Li, D P. Wildes, M Singh, E S. Koltun, A L. Gill, J A. Smith. Discovery of RMC-6291, a tri-complex KRASG12C(ON) inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr ND07.
The Devil Is in the Detail: Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty
Authors: Gillian A. Hawker
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march
Authors: Inge Kortekaas Krohn, Fariza Mishaal Saiema Badloe, Nadine Herrmann, Laura Maintz, Shauni De Vriese, Johannes Ring, Thomas Bieber, Jan Gutermuth
Journal: Allergy (2023)

Abstract Background Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples ( n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years). Methods Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” ( n = 115). Also, subjects without AD but with Type‐2 diseases (“atopic controls,” n = 52) and non‐atopic “healthy controls” ( n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Results Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets. Conclusions Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.
State Restrictions and Geographic Access to Gender-Affirming Care for Transgender Youth
Authors: Luca Borah, Laura Zebib, Hayley M. Sanders, Megan Lane, Daphna Stroumsa, Kevin C. Chung
Journal: JAMA (2023)

This study estimates changes in geographic access and drive times to gender clinics following legislation enacted to restrict puberty-suppressing medications and hormones for those younger than 18 years.
Trends in Cardiovascular Health Counseling Among Postpartum Individuals
Authors: Natalie A. Cameron, Lynn M. Yee, Brigid M. Dolan, Matthew J. O’Brien, Philip Greenland, Sadiya S. Khan
Journal: JAMA (2023)

Importance Poor prepregnancy cardiovascular health (CVH) and adverse pregnancy outcomes (APOs) are key risk factors for subsequent cardiovascular disease (CVD) in birthing adults. The postpartum visit offers an opportunity to promote CVH among at-risk individuals. Objective To determine prevalence, predictors, and trends in self-reported CVH counseling during the postpartum visit. Design, Setting, and Participants Serial, cross-sectional analysis of data from 2016-2020 from the Pregnancy Risk Assessment Monitoring System (PRAMS), a nationally representative, population-based survey. The primary analysis included individuals who attended a postpartum visit 4 to 6 weeks after delivery with available data on receipt of CVH counseling, self-reported prepregnancy CVD risk factors (obesity, diabetes, and hypertension), and APOs (gestational diabetes, hypertensive disorders of pregnancy, and preterm birth) (N = 167 705 [weighted N = 8 714 459]). Exposures Total number of CVD risk factors (0, 1, or ≥2 prepregnancy risk factors or APOs). Main Outcomes and Measures Annual, age-adjusted prevalence of self-reported postpartum CVH counseling per 100 individuals, defined as receipt of counseling for healthy eating, exercise, and losing weight gained during pregnancy, was calculated overall and by number of CVD risk factors. Average annual percent change (APC) assessed trends in CVH counseling from 2016 through 2020. Data were pooled to calculate rate ratios (RRs) for counseling that compared individuals with and without CVD risk factors after adjustment for age, education, postpartum insurance, and delivery year. Results From 2016 through 2020, prevalence of self-reported postpartum CVH counseling declined from 56.2 to 52.8 per 100 individuals among those with no CVD risk factors (APC, −1.4% [95% CI, −1.8% to −1.0%/y]), from 58.5 to 57.3 per 100 individuals among those with 1 risk factor (APC, −0.7% [95% CI, −1.3% to −0.1%/y]), and from 61.9 to 59.8 per 100 individuals among those with 2 or more risk factors (APC, −0.8% [95% CI, −1.3% to −0.3%/y]). Reporting receipt of counseling was modestly higher among individuals with 1 risk factor (RR, 1.05 [95% CI, 1.04 to 1.07]) and with 2 or more risk factors (RR, 1.11 [95% CI, 1.09 to 1.13]) compared with those who had no risk factors. Conclusions and Relevance Approximately 60% of individuals with CVD risk factors or APOs reported receiving CVH counseling at their postpartum visit. Prevalence of reporting CVH counseling decreased modestly over 5 years.
Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women
Authors: Art Schuermans, Tetsushi Nakao, Md Mesbah Uddin, Whitney Hornsby, Shriie Ganesh, Aladdin H. Shadyab, Simin Liu, Bernhard Haring, Chrisandra L. Shufelt, Margaret A. Taub, Rasika A. Mathias, Charles Kooperberg, Alexander P. Reiner, Alexander G. Bick, JoAnn E. Manson, Pradeep Natarajan, Michael C. Honigberg
Journal: Circulation Research (2023)

Premature menopause is a risk factor for accelerated cardiovascular aging, but underlying mechanisms remain incompletely understood. This study investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease. Participants from the UK Biobank and Women's Health Initiative with complete reproductive history and LTL measurements were included. Primary analyses tested the association between age at menopause and LTL using multivariable-adjusted linear regression. Secondary analyses stratified women by history of gynecologic surgery. Mendelian randomization was used to infer causal relationships between LTL and age at natural menopause. Multivariable-adjusted Cox regression and mediation analyses tested the joint associations of premature menopause and LTL with incident coronary artery disease. This study included 130 254 postmenopausal women (UK Biobank: n=122 224; Women's Health Initiative: n=8030), of whom 4809 (3.7%) had experienced menopause before age 40. Earlier menopause was associated with shorter LTL (meta-analyzed ß=-0.02 SD/5 years of earlier menopause [95% CI, -0.02 to -0.01]; P=7.2×10-12). This association was stronger and significant in both cohorts for women with natural/spontaneous menopause (meta-analyzed ß=-0.04 SD/5 years of earlier menopause [95% CI, -0.04 to -0.03]; P<2.2×10-16) and was independent of hormone therapy use. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. LTL and age at menopause were independently associated with incident coronary artery disease, and mediation analyses indicated small but significant mediation effects of LTL in the association of menopausal age with coronary artery disease. Earlier age at menopause is associated with shorter LTL, especially among women with natural menopause. Accelerated telomere shortening may contribute to the heightened cardiovascular risk associated with premature menopause.
Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course
Authors: Ji Soo Kim, Adrianne Woods, Laura Gutierrez‐Alamillo, Maureen Laffoon, Fredrick M. Wigley, Laura K. Hummers, Antony Rosen, Scott Zeger, Robyn T. Domsic, Livia Casciola‐Rosen, Ami A. Shah
Journal: Arthritis & Rheumatology (2023)

We examined whether an array of scleroderma autoantibodies associates with risk of cancer and could be useful tools for risk stratification.
Insights into Stevens–Johnson syndrome/toxic epidermal necrolysis lifetime burden: assessing life expectancy, healthcare costs and quality of life
Authors: Yi Liu, Qing Li, Chenyu Chu, Yin Zhou
Journal: British Journal of Dermatology (2023)

This study highlights the need for further exploration of factors that influence the declining incidence rate of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), interventions to mitigate loss-of-life expectancy and healthcare costs, and impact on quality of life. The findings emphasize the importance of ongoing efforts to minimize the burden of SJS/TEN and optimize patient care.
Verapamil and Pancreatic Beta Cell Function in Pediatric Type 1 Diabetes
Authors: Nin-Chieh Hsu, Hung-Bin Tsai, Chia-Hao Hsu
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Research and Nonresearch Industry Payments to Nephrologists in the United States between 2014 and 2021
Authors: Anju Murayama, Sae Kamamoto, Hinari Kugo, Hiroaki Saito, Akihiko Ozaki
Journal: Journal of the American Society of Nephrology (2023)

Concerns about the financial relationships between nephrologists and the health care industry have been reported in the United States over the past decade. However, since the 2014 launch of the federal transparency database, Open Payments, few documents have explored the whole picture of research and nonresearch payments to US nephrologists from industry sources. In this study, the authors found that 87% of nephrologists have received nonresearch payments, and the aggregate amount of these payments has been increasing since 2014. Only 12% of nephrologists received research payments; these recipients were disproportionately male. In addition, the top 5% of nephrologists receiving nonresearch funds received 81% of all such payments. Nonresearch payments were larger among male nephrologists than among female nephrologists and increased by 8% annually among male nephrologists between 2014 and 2019.
Colorectal Cancer Organoid–Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses
Authors: Henner F. Farin, Mohammed H. Mosa, Benardina Ndreshkjana, Britta M. Grebbin, Birgit Ritter, Constantin Menche, Kilian B. Kennel, Paul K. Ziegler, Lili Szabó, Julia Bollrath, Dietmar Rieder, Birgitta E. Michels, Alena Kress, Müge Bozlar, Tahmineh Darvishi, Sara Stier, Ivan-Maximilano Kur, Katrin Bankov, Rebecca Kesselring, Stefan Fichtner-Feigl, Bernhard Brüne, Thorsten O. Goetze, Salah-Eddin Al-Batran, Christian H. Brandts, Wolf O. Bechstein, Peter J. Wild, Andreas Weigert, Susanne Müller, Stefan Knapp, Zlatko Trajanoski, Florian R. Greten
Journal: Cancer Discovery (2023)

In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived tumor organoids (PDTO) show enormous potential for preclinical testing; however, cultured tumor cells lose important characteristics, including the consensus molecular subtypes (CMS). To better reflect the cellular heterogeneity, we established the colorectal cancer organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that xenotransplantation or coculture with CAFs improves the transcriptomic fidelity and instructs subtype-specific stromal gene expression. Furthermore, functional profiling in coculture exposed CMS4-specific therapeutic resistance to gefitinib and SN-38 and prognostic expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as a common target. Our results demonstrate that colorectal cancer phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for a faithful representation of molecular subtypes and therapy responses ex vivo. Systematic characterization of the organoid-stroma biobank provides a resource for context dependency in colorectal cancer. We demonstrate a colorectal cancer subtype memory of PDTOs that is independent of specific driver mutations. Our data underscore the importance of functional profiling in cocultures for improved preclinical testing and identification of stromal resistance mechanisms. This article is featured in Selected Articles from This Issue, p. 2109.
Antibiotic Prescription for Outpatients With COVID-19 in Primary Care Settings in Japan
Authors: Atsushi Miyawaki, Kei Kitajima, Akihiro Iwata, Daichi Sato, Yusuke Tsugawa
Journal: JAMA Network Open (2023)

This cross-sectional study assesses the characteristics of patients and physicians associated with antibiotic prescription for COVID-19.
Worldwide trends in esophageal cancer survival, by sub‐site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000‐2014 (CONCORD‐3)
Authors: Melissa Matz, Mikhail Valkov, Mario Šekerija, Sabine Luttman, Adele Caldarella, Michel P Coleman, Claudia Allemani
Journal: Cancer Communications (2023)

Esophageal cancer survival is poor worldwide, though there is some variation. Differences in the distribution of anatomical sub-site and morphological sub-type may help explain international differences in survival for all esophageal cancers combined. We estimated survival by anatomic sub-site and morphological sub-type to understand further the impact of topography and morphology on international comparisons of esophageal cancer survival.We estimated age-standardized one-year and five-year net survival among adults (15-99 years) diagnosed with esophageal cancer in each of 60 participating countries to monitor survival trends by calendar period of diagnosis (2000-2004, 2005-2009, 2010-2014), sub-site, morphology, and sex.For adults diagnosed during 2010-2014, tumors in the lower third of the esophagus were the most common, followed by tumors of overlapping sub-site and sub-site not otherwise specified. The proportion of squamous cell carcinomas diagnosed during 2010-2014 was generally higher in Asian countries (50%-90%), while adenocarcinomas were more common in Europe, North America and Oceania (50%-60%). From 2000-2004 to 2010-2014, the proportion of squamous cell carcinoma generally decreased, and the proportion of adenocarcinoma increased. Over time, there were few improvements in age-standardized five-year survival for each sub-site. Age-standardized one-year survival was highest in Japan for both squamous cell carcinoma (67.7%) and adenocarcinoma (69.0%), ranging between 20%-60% in most other countries. Age-standardized five-year survival from squamous cell carcinoma and adenocarcinoma was similar for most countries included, around 15%-20% for adults diagnosed during 2010-2014, though international variation was wider for squamous cell carcinoma. In most countries, survival for both squamous cell carcinoma and adenocarcinoma increased by less than 5% between 2000-2004 and 2010-2014.Esophageal cancer survival remains poor in many countries. The distributions of sub-site and morphological sub-type vary between countries, but these differences do not fully explain international variation in esophageal cancer survival.
Ectopic Pregnancy Risk and Levonorgestrel-Releasing Intrauterine Systems—Reply
Authors: Amani Meaidi, Christian Torp-Pedersen, Lina Steinrud Mørch
Journal: JAMA (2023)

In Reply In response to the comments from Mr Jugl and Dr Winterstein, our Research Letter1 addressed the potential of early discontinuation of levonorgestrel-releasing IUSs through sensitivity analyses with different definitions of duration of IUS use.